OBSiDiAN in a Stapled Circular Esophagogastric Anastomosis After Ivor Lewis Esophagectomy

Evaluation of Effectiveness and Safety of Autologous BioMatrix OBSiDiAN to Enhance a Stapled Circular Esophagogastric Anastomosis After Ivor Lewis Esophagectomy in a Multicentre Randomized Controlled Trial.

Multicentre randomized controlled trial to evaluate the effectiveness of an autologous BioMatrix on a circular stapled esophagogastric anastomosis after Ivor Lewis esophagectomy.

Study Overview

• Status: Withdrawn
• Conditions: Anastomotic Leak Esophagus
• Intervention / Treatment: Device: Obsidian

Detailed Description

STUDY PRODUCT Autologous BioMatrix: Obsidian (medical device class III)

STUDY POPULATION Subjects ≥ 18 years and ≤ 75 years of age scheduled for elective Ivor Lewis esophagectomy for oesophageal cancer with a circular stapled intrathoracic esophagogastric anastomosis.

SAMPLE SIZE A total of 600 patients will be included in the study. 300 patients in each study arm.

ENROLEMENT PERIOD Based on an annual number of 70-80 esophagectomies in this centre, University Hospital Ghent, with inclusion of patients in other European high volume centers, we predict an enrolment period of 4 years.

PRIMARY ENDPOINT Anastomotic leak type I, II and III within 30 days post operatively. Anastomotic leak is defined according to the Esophagectomy Complications Consensus Group (ECCG).

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

preoperatively

• Subjects ≥ 18 years and ≤ 75 years who are willing to participate and provide written informed consent prior to any study-related procedures.
• Subjects with oesophageal carcinoma scheduled for elective minimally invasive or open Ivor Lewis esophagectomy Intra-operatively
• intrathoracic circular stapled esophagogastric anastomosis

Exclusion Criteria:

preoperatively

• Female patients who are pregnant or nursing
• Participation in another study involving investigational drugs or devices.
• Use of Avastin within 30 days prior to surgery
• ASA IV (American Society of Anesthesiologists physical status classification system: patient with severe systemic disease that is a constant threat to life)
• Patients with other malignancies
• Patients with previous esophageal or gastric surgery
• Known hypersensitivity to batroxobin and tranexamic acid.
• Hemoglobin level < 8 g/dL
• Patients on medicine containing acetylsalicylic acid not able to stop using the medicine for medical reasons 3 days before taking the blood sampling.
• Patients on clopidogrel not able to stop clopidogrel for medical reasons 7 days before blood sampling
• Patients on other platelet aggregation inhibitor therapies not able to stop using the platelet aggregation inhibitor therapies for 3 days before taking the blood sample.

Intra-operatively

• Intra-operative findings that may preclude conduct of the study procedures, such as pleural metastasis, tumor invasion in other organs, …
• Anastomosis preformed differently than the standard of care
• Excessive bleeding (>500 ml) prior to anastomosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: study group; For the study group, a unit of autologous BioMatrix OBSiDiAN will be produced. Blood sample (120ml) will be taken after randomization at the ending of the abdominal phase of the surgery. The surgeon will create an esophagogastric anastomosis, after ruling out tension or torsion. Around 1-2ml of autologous BioMatrix OBSiDiAN will be applied on the distal/or proximal resection stump before the stapled anastomose will be created. After firing the standard circular device and creation of a functional anastomosis, a further 2.5-3ml OBSiDiAN must be applied circumferentially on the outside on the anastomosis. Once application is completed, a 30 seconds waiting period is required before putting the esophagus back into the surgical field (study specific). A methylene blue leakage test or other leakage test is performed (standard of care). If there is a leak, the anastomosis will be corrected or the completed procedure has to be done again.	Device: Obsidian; To create OBSiDiAN BioMatrix, 120 ml of the the patient's blood is added to the processing unit. The Vivostat® processor unit heats, separates, centrifugates to get the plasma. Batroxobin is added. After again processing, the result is an OBSiDian syringe filled with BioMatrix Obsidian®ASG. This will be applied on the anastomosis
No Intervention: standard group; The surgeon will create an esophagogastric anastomosis, after ruling out tension or torsion. A methylene blue leakage test or other leakage test is performed (standard of care). If there is a leak, the anastomosis will be corrected.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anastomotic leak	Anastomotic leak defined according to the ECCG guidelines type I: local defect requiring no change in therapy or treated medicallly or with dietary modifications type II: localized defect requiring interventional but not surgical therapy, for example, interventional radiology drain, stent or bedside opening and packing or incision type III: localized defect requiring surgical therapy	Absence of anastomotic leak within 30 days post operatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mortality	in hospital mortality	from surgery until 30 days post operative
sepsis	in hospital sepsis	from surgery until 30 day post operative
pneumonia	in hospital pneumonia	from surgery until 30 day post operative
stricture	stricture of the esophagogastric anastomosis	from surgery until 1 year post operative
ICU stay	length of ICU stay	from surgery until discharge or until the date of death from any cause, whichever came first, assessed up to 3 months
hospital stay	total hospital stay	from surgery until discharge or until the date of death from any cause, whichever came first, assessed up to 3 months
thoracic drainage volume	Volume of thoracic drain	from surgery until removal of thoracic drain within the first week postoperative
thoracic drainage duration	duration of thoracic drain	from surgery until removal of thoracic drain within the first week postoperative
late anastomotic leakage	late anastomotic leakage (ECCG type I, II and III)	from surgery until 90 days post operative
inflammation WBC	post operative inflammation (WBC)	from date of randomisation to postoperative day 5
inflammation CRP	post operative inflammation (CRP)	from date of randomisation to postoperative day 5

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Investigators: Principal Investigator: Piet Pattyn, UZ Gent

Publications and helpful links

General Publications

• Plat VD, Bootsma BT, van der Wielen N, van der Peet DL, Daams F. Autologous Activated Fibrin Sealant for the Esophageal Anastomosis: A Feasibility Study. J Surg Res. 2019 Feb;234:49-53. doi: 10.1016/j.jss.2018.08.049. Epub 2018 Sep 27.

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: November 8, 2021
• First Submitted That Met QC Criteria: February 1, 2023
• First Posted (Actual): February 6, 2023

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Anastomotic Leak
• Other Study ID Numbers: BC-09974

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No